title: Concentration polarization of ox-LDL activates autophagy and apoptosis via regulating LOX-1 expression.
abstract: Here we demonstrate that "concentration polarization" of ox-LDL enhances LOX-1 expression and ox-LDL uptake. It damages cell surface heparan sulfate proteoglycans (HSPG) and activates LOX-1 dependent autophagy and apoptosis. We also show that ox-LDL concentration polarization occurs on the surface of rabbit thoracic aorta and induces autophagy and apoptosis. In order to investigate the significance of swirling flow on LOX-1 expression, HSPG damage, autophagy and apoptosis in the arterial system, an ex vivo model of swirling flow was developed. We observed that swirling flow decreases relative wall concentration of ox-LDL, inhibits LOX-1 expression, protects HSPG from damage, and decreases both autophagy and apoptosis. Taken together, our data suggest that ox-LDL concentration polarization plays an important role in the localization of atherosclerotic lesions concomitant with LOX-1 dependent autophagy and apoptosis. These observations also suggest a novel mechanism by which swirling flow in the arterial system protects arterial wall from atherogenesis.
authors.affiliation: Central Arkansas Veterans Healthcare System and the Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Zufeng
authors.initials: Z
authors.lastname: Ding
authors.forename: Shijie
authors.initials: S
authors.lastname: Liu
authors.forename: Changqing
authors.initials: C
authors.lastname: Sun
authors.forename: Zengsheng
authors.initials: Z
authors.lastname: Chen
authors.forename: Yubo
authors.initials: Y
authors.lastname: Fan
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Deng
authors.forename: Xianwei
authors.initials: X
authors.lastname: Wang
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D017209:Apoptosis; D001343:Autophagy; D002478:Cells, Cultured; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D051127:Scavenger Receptors, Class E / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein